Slowing of peripheral motor nerve conduction was ameliorated by aminoguanidine in streptozocin-induced diabetic rats.

The aims of this study were to investigate the effect of aminoguanidine (AG) on slowing of motor nerve conduction velocity (MNCV) of the sciatic nerve in streptozocin-induced diabetic rats and to assess its mechanism of action. The MNCV of the sciatic nerve was measured electrophysiologically in diabetic rats treated with and without AG for 16 weeks. To elucidate the action of AG, morphological lesion and abnormality of polyol pathway metabolism in the nerve were examined and tissue levels of advanced glycosylation end-products (AGE) were determined as an indicator of AGE accumulation in tissue. Diabetic rats were treated with AG at three doses of 10, 25 and 50 mg/kg for 16 weeks. Myelinated fiber morphometry and nerve Na+,K(-)-ATPase activity were determined. The AGE levels in renal cortex were measured by a specific ELISA. Aminoguanidine dose-dependently ameliorated slowing of MNCV 16 weeks after the treatment without changing body weight or blood glucose levels. No difference in myelinated fiber morphometry or Na+,K(+)-ATPase activity with or without AG treatment was detected in diabetic rats. Diabetes increased the AGE level in the renal cortex by six times compared to non-diabetic rats, and AG reduced the rise in the AGE level by 40%. The MNCV was inversely correlated with the AGE levels. We conclude that improvement of conduction slowing by AG in experimental diabetes may be through decreasing the AGE level in the peripheral tissues. Aminoguanidine may have a therapeutic potential in controlling diabetic peripheral neuropathy.

Transport and metabolism of glutathione isopropyl ester in cerebrospinal fluid.

The transport of glutathione (GSH) or glutathione isopropyl ester (GSH isopropyl ester) to the cerebrospinal fluid (CSF) in rats was estimated by levels of GSH or GSH isopropyl ester and their metabolites in CSF 30 min after the intravenous administration of GSH or GSH isopropyl ester (300 mg/kg). Although the CSF uptake of GSH isopropyl ester was almost equal to that of GSH as evidenced by about a two-fold increase in the amount of non-protein sulfhydryl groups in CSF, the sum of GSH isopropyl ester and GSH concentrations in the CSF after GSH isopropyl ester treatment was increased by 32% compared with saline-treated controls. On the other hand, treatment with GSH had no significant increase in GSH levels in CSF but increased its metabolite levels, such as cysteinyl-glycine and cysteine. GSH isopropyl ester was less metabolized than GSH. GSH isopropyl ester had low affinity to purified gamma-glutamyl transpeptidase, a key enzyme for metabolism of GSH in the choroid plexus, supporting the finding that GSH isopropyl ester is more stable than GSH in CSF. These results are compatible with our previous report (Yamamoto et al. (1993) showing that the protective action of GSH isopropyl ester against cerebral ischemia was greater than that of GSH in rats. GSH isopropyl ester may be a useful agent which protects the brain from the damage associated with oxygen-related toxicities by increasing GSH levels in the CSF.

[Pulmonary complications in patients with rheumatoid arthritis].

Pulmonary manifestations of rheumatoid arthritis were studied in 26 patients. Pulmonary complications could be divided into four subgroups: Interstitial pneumonia/Pulmonary fibrosis (n = 18), Bronchiolitis Obliterans Organizing Pneumonia (n = 4), Bronchiolitis Obliterans (n = 2), and Pleuritis/Pericarditis (n = 1). Analysis of cells in broncho-alveolar lavage fluid (BALF) revealed abnormally high percentages of lymphocytes in one-half of the patients and abnormally high percentages of neutrophils in one-third of the patients. The percent of BALF cells that were neutrophils was higher with higher chest radiograph grades. Analysis of soluble constituents of BALF indicated local production of IgG in two cases, but IgM-rheumatic factor was not detected. In 18 of 26 patients corticosteroid or immunosuppressive drugs were needed, and most of the patients responded to the therapy and had good outcomes. The conditions of 6 patients with interstitial pneumonia/pulmonary fibrosis deteriorated and 4 patients died of progressive respiratory failure. The subclassification of rheumatoid lung was useful for predicting its outcome.

[Prognosis of idiopathic interstitial pneumonia].

Idiopathic interstitial pneumonia (IIP) is characterized by chronic inflammation and fibrosis of the lung. It carries a poor prognosis and the treatment for IIP has not yet been established. We evaluated 116 cases of IIP retrospectively, and analyzed possible prognostic factors, such as the mode of detection, clinical symptoms, chest X-ray findings, pulmonary function tests, blood chemistry, bronchoalveolar lavage (BAL), and treatments. The 5-year survival rate from the onset was 39.5% and the 10-year survival rate was only 12.7%. The 5-year survival rate from the appearance of dyspnea on exertion was 23.2% and 10-year survival rate was 9.0%. According to the results of the Kaplan-Meier analysis, patients with low% FVC (< 70%), those with high values of ESR, those with high values of CRP, and those with advanced chest X-ray shadows did not survive as long as other patients. Multivariate analysis with a proportional hazards model revealed that a high percentage of eosinophils in BALF was associated with a poor prognosis. Analysis with a logistic model revealed that being male having a low %DLCO were associated with a poor prognosis.

[A case of subcutaneous sarcoid nodules induced by interferon-alpha].

A 57-year-old woman came to our hospital complaining of multiple subcutaneous nodules that developed while she received corticosteroid therapy for pulmonary sarcoidosis. She was treated with interferon-alpha (IFN-alpha) at another hospital for C-type chronic hepatitis and she noticed these nodules with tenderness two months after treatment began. A biopsy specimen of the nodule revealed subcutaneous sarcoid granuloma. Her abnormally high serum-ACE value and subcutaneous nodules resolved after the dose of IFN-alpha was gradually reduced. IFN therapy should be used with care in cases of sarcoidosis in which IFN-gamma and T-lymphocytes are mainly involved.

[Hypersensitivity pneumonitis--histopathology of summer-type hypersensitivity pneumonitis].

Summer-type hypersensitivity pneumonitis(SHP) first reported by T. OCHI, et al. (1978), as a new type hypersensitivity pneumonitis(HP) with features of initiation during summer and anti-Cryptococcus antibody positive sera, has been recognized as "a unique disease in Japan", a most common type of HP in Japan, and now also known as anti-Trichosporon cutaneum antibody-positive SHP. This report was mainly concerned with the histopathology of SHP, thus far diagnosed in our hospital. Of the cases in our hospital, 62 consecutive biopsied cases (3 cases of open lung biopsy and 59 cases of transbronchial lung biopsy) without steroid institution before lung biopsy have been reviewed and revealed granulomatous interstitial pneumonitis in the bronchiolo-alveolar region, like various types of HP. Alveolitis (61 of 62 cases; 98.4%), sarcoid-like granuloma (50 of 62; 80.6%) and Masson's body (36 of 62; 58.1%) are main features, and could be named "triad" features. Concerning histopathological findings related with the period of lung biopsy after onset of clinical episodes as HP, alveolitis has been present regardless of period, and fibrinous exudate present in the early period and not in a case at 4 months. Sarcoid-like granuloma and Masson's body have appeared firstly at one-month cases. After this period sarcoid-like granuloma have been present in nearly all cases, but Masson's body has been not present in 10-month case with gradual decrease after 2 months, when all 2-month cases had it. In summary, for histopathological diagnosis of HP, the "triad" features and the time of lung biopsy done are keys, taking into consideration histopathological differential diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

[Specific antibody-forming cells in bronchoalveolar lavage fluid of patients with summer-type hypersensitivity pneumonitis--detection by enzyme-linked immunospot (ELISPOT)].

Antigen-specific antibody-forming cells (AFCs) were assessed in bronchoalveolar lavage (BAL) fluid of patients with summer-type hypersensitivity pneumonitis by the method of enzyme-linked immunospot (ELISPOT). Both Cryptococcus- and Trichosporon-specific AFCs of isotypes of IgG, IgA and IgM were detected in BAL fluid cells. The frequency of isotypes of AFCs was in the order of IgA > IgM > IgG. Antibody activities against both Cryptococcus and Trichosporon antigens were detected in the culture supernatant of BAL cells. A good correlation was observed between the number of AFCs and the degree of antibody activity of culture supernatant of BAL cells, particularly of IgA isotype. For the IgM and IgA isotypes, anti-Cryptococcus antibody activity correlated well with anti-Trichosporon antibody activity (r = 0.98, p < 0.0001). In several cases examined, antigen-specific AFCs were detected in in vitro culture of peripheral blood mononuclear cells of patients after stimulation with PWM. In the present study, we demonstrated that Cryptococcus neoformans and Trichosporon cutaneum antigen-specific AFCs were present in the lungs of patients with summer-type hypersensitivity pneumonitis, and the antibodies secreted therefrom reacted with both these antigens. The presence of memory B cells was also suggested in the peripheral blood of patients.

[A case of multiple broncholithiasis caused by mucus retention].

The patient was a 57-year-old male with long-standing bronchiectasis who developed severe respiratory failure and died in 1991. Autopsy revealed multiple broncholithiasis in both lungs, but no calcified lymph nodes in the hilar region. Since histological examination of the broncholiths showed only stratified structures but no tissue structure, most likely cause was considered to be calcification of mucus in the bronchi. Analysis of the stone components revealed 78% calcium and 22% protein. This patient represents a case of multiple broncholithiasis caused by mucus retention, which is thought to be very rare.

[The introduction of home mechanical ventilation in Japan].

In the same context as home oxygen therapy in Japan, there is an urgent need to establish a home mechanical ventilation (HMV) support system for clinically stable patients dependent on long-term mechanical ventilation who wish to spend their lives outside institutions; at home in the community. We have cared for 3 HMV cases as long as 8, 5 and 2 years. All patients suffer from respiratory muscle paralysis with chronic neuromuscular diseases and require CMV mode mechanical ventilation for 18 to 24 hours/day using electrically drived portable ventilators connected to a tracheostomy tube. They need no oxygen supplementation. All patients clearly expressed a desire for the life style with HMV. Their families as the main caregivers willingly received the necessary training and mastered the techniques quickly, including AMBU-bag manual ventilation for occasional ventilator troubles, and bronchial hygiene. Our experiences of three HMV cases may be local and limited, but reveal the potential significance and technological possibility for home application of the care techniques that have been developed on or in-patient basis. The nationwide surveys of the status of patients requiring long-term mechanical ventilation for more than 3 months of duration by Suetsugu et al. (supported by Respiratory Failure Research Council of Health and Welfare Ministry) (1987, 1988 and 1989) listed 53 HMV cases in 1989 and revealed a slowly increasing trend from the 17 cases in 1987. However, it is important to recognize that the true medicosocial establishment of HMV in Japan is still behind and should be an urgent goal of respiratory care programs.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of nicardipine on ischemic mechanical failure and tissue injury in isolated perfused rat heart.

Using a Langendorff rat heart preparation, we examined effects of nicardipine, a calcium channel blocker, on different stages of ischemic damage, characterized by a development of contracture and leakage of intracellular enzymes. Maximum recoveries of heart rate (HR) and peak left ventricular pressure-HR product after 20 min ischemia were attenuated by about 25% compared with those before ischemia. When nicardipine (0.1 mumol) was added to the perfusate 5 min prior to ischemia, this mechanical failure recovered completely to the pre-ischemic level. Although a significant increase in left ventricular end-diastolic pressure was observed in hearts exposed to 30 min ischemia, the amount of creatine kinase (CK) released during re-flow after 30 min ischemia was not enhanced by contracture but was proportional to the duration of ischemia (compared with that of 20 min ischemia). Nicardipine reduced CK leakage by 25% after 30 min ischemia but did not alter either ATP levels or coronary flow. The beneficial effects of nicardipine on ischemic damage are probably related to inhibition of calcium influx (Terai et al: Biochem Pharmacol 30: 375, 1981), which may accompany reperfusion of ischemic myocardium.